In recent years, various bone diseases such as osteoporosis, bone fractures, and lumbago have increased along with the progressive increase in the elderly population. In a bone tissue, osteogenesis and bone resorption constantly occur. In a young person, a balance between osteogenesis and bone resorption is kept, but the balance is disrupted to bone resorption owing to various causes with aging (uncoupling). Continuance of this state for a long period of time makes the bone tissue fragile, resulting in occurrence of various bone diseases such as osteoporosis, bone fractures, and lumbago. It is considered that prevention of the uncoupling enables prevention of various bone diseases such as osteoporosis, bone fractures, and lumbago.
Conventionally, to prevent the uncoupling and to prevent or treat various bone diseases such as osteoporosis, bone fractures, and lumbago, the following methods have been performed: (1) calcium supplementation by diet, (2) light exercise, (3) insolation, (4) medication, and the like. For calcium supplementation by diet, there are used calcium salts such as calcium carbonate and calcium phosphate and natural calcium agents such as eggshell and fish bone powder. However, they are not completely suitable materials for oral ingestion. For light exercise, it is said that jogging or walking is good. However, a person whose body has weakened tends to think very troublesome to perform even light exercise, and a bedridden elderly is scarcely able to exercise. Insolation is said to be good in the light of supplementation of activated vitamin D3. However, even if only insolation is performed, only insufficient effects are obtained. For administration of a drug, there are used 1-α-hydroxyvitamin D3, a calcitonin preparation, and the like, which are known to be effective for treating osteoporosis. However, those substances are drugs themselves and cannot be used as food materials.
On the other hand, the inventors of the present invention have searched for an osteogenesis promoting factor and a bone resorption inhibiting factor in milk to obtain substances that have an osteogenesis promoting effect and a bone resorption inhibiting effect and can be used as food materials. In the process, the inventors of the present invention have found out that lactoperoxidase promotes osteoblast differentiation to have an osteogenesis promoting effect. The osteoblast is a cell playing a major role in osteogenesis, which is present on the surface of a bone tissue and secretes bone matrix proteins. Crystals of calcium phosphate are deposited on the bone matrix proteins to form hard bone tissues.
On the other hand, an osteoclast is a cell that is generated from a hematopoietic stem cell, which is present on the surface of a spongy bone and dissolves the bone. It is considered that an osteoclast dissolves a bone matrix (bone resorption), and then an osteoblast synthesizes a bone matrix, resulting in occurrence of bone formation, growth (modeling), or metabolism (remodeling). The invention of the present application has been found out that lactoperoxidase promotes differentiation of an osteoblast that plays a major role of osteogenesis in the bone metabolism to have an osteogenesis promoting effect and to have a bone strengthening effect.
Lactoperoxidase is present in milk in large amounts and is a glycoprotein that contains heme iron and has a molecular weight of about 80,000. The lactoperoxidase content in bovine milk is higher than that in human milk. The content in human milk is 0.01 mg/100 ml or less, while the content in bovine milk is about 3 mg/100 ml. A function of lactoperoxidase includes oxidation of various substances in the presence of hydrogen peroxide. That is, hypothiocyanate (OSCN−) generated in the case of oxidation of thiocyanate (SCN−) by lactoperoxidase inhibits proliferation of a certain kind of microorganism. SCN− is a metabolite in a living body and is generally present in milk, so that proliferation of a microorganism producing hydrogen peroxide is inhibited by lactoperoxidase in milk. As described above, lactoperoxidase is considered to act as one of antibacterial effects of milk, which is also referred to as a lactoperoxidase system. With regard to use of lactoperoxidase, there are known a technique to maintain an appropriate sourness of a product during the best-before period by blending lactoperoxidase in fermented milk to suppress excessive increase in the sourness during circulation and preservation of the product (see, for example, Patent Document 1), an aging preventing agent (see, for example, Patent Document 2), a low cariogenic nutritive agent (see, for example, Patent Document 3), an agent for treatment of animal dermatosis (see, for example, Patent Document 4), and the like. However, the fact that lactoperoxidase has an osteoblast differentiation promoting effect has not been clarified yet, and therefore lactoperoxidase is not used for bone strengthening.
For a bone strengthening effect of milk, the inventors of the present invention have found out that basic proteins, which are present in minute amounts in milk, have an osteoblast proliferation promoting effect, a bone strengthening effect, and a bone resorption inhibiting of effect, and they have applied for a patent (see, for example, Patent Document 5). However, it is not known that lactoperoxidase contained in the basic proteins has an osteogenesis promoting effect.    Patent Document 1: WO 92/13064    Patent Document 2: JP 05-124980 A    Patent Document 3: JP 09-107917 A    Patent Document 4: JP 07-233086 A    Patent Document 5: JP 08-151331 A